Abnormalities of the cell membrane and cell surface of tumor cells contribute to their escape from many of the controls and social restraints to which normal cells are subject. Although a wide range of information is available about the surface structure and composition of normal and neoplastic cells in culture, cell surfaces within epithelia are relatively inaccessible to the tools utilized to study single cells. Consequently, little is known about the biochemical composition and structure of cell membranes and surfaces within epithelia. The studies proposed here, utilizing the recently isolated and purified staphylococcal epidermolytic toxin, will permit direct visualization and manipulation of viable cell surfaces within epithelia. This substance causes mid-epithelial separation of human and murine skin both in vivo and in vitro, without cytolysis or removal of several surface coat materials. Exposed surfaces of normal and neoplastic epithelia will be fixed immediately in situ, dehydrated, and critical point dried. Platinum-carbon and gold-palladium replicas will be examined by transmission and scanning electron microscopy respectively. Furthermore, the functional properties of the exposed cell surfaces will be studied using lectin binding and enzyme treatment prior to fixation. Finally, integral membrane particle organization in relation to surface structure will be analyzed with a combination of freeze-fracture and freeze-etch methods. One purpose of these studies will be to determine the relevance of studies on neoplastic cultured cells to cancer cells in vivo. In addition, the information generated from these studies will provide new information about malignant cell membranes in vivo, and may suggest new avenues whereby the surfaces of neoplastic cells can be experimentally modified in order to control tumor growth.